Jehannine Austin

Prenatal Exposure to Maternal Depressed Mood and the MTHFR C677T Variant Affect SLC6A4 Methylation in Infants at Birth

Background Prenatal and early postnatal exposure to maternal depression may “program” childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour. Methods/Principal Findings Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2nd and 3rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2nd trimester depressed mood (p<0.05). Increased 2nd trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation. Conclusions These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.

Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools

Abstract. At present, the cost of genotyping single nucleotide polymorphisms (SNPs) in large numbers of subjects poses a formidable problem for molecular genetic approaches to complex diseases. We have tested the possibility of using primer extension and denaturing high performance liquid chromatography to estimate allele frequencies of SNPs in pooled DNA samples. Our data show that this method should allow the accurate estimation of absolute allele frequencies in pooled samples of DNA and also of the difference in allele frequency between different pooled DNA samples. This technique therefore offers an efficient and cheap method for genotyping SNPs in large case-control and family-based association samples.

Genotyping single nucleotide polymorphisms by primer extension and high performance liquid chromatography

We have investigated the possibility of genotyping single nucleotide polymorphisms (SNPs) by primer extension and high performance liquid chromatography (HPLC). Using three polymorphisms of current interest to our group (an A/G polymorphism in the proneurotensin gene and A/G and T/C polymorphisms in the 5HT2a receptor gene), we show that robust signal is obtained using this simple analytic method which has the added advantages that sample loading and analysis are essentially automated, analytic time is brief, and no further purification step after primer extension is required. We also show that all stages of the HPLC-primer extension genotyping can be multiplexed which, together with automation, suggests that this system may be suitable for linkage studies based upon emerging SNP maps.

Schizophrenia: An Update and Review

Schizophrenia is a common complex disorder characterized by psychosis, cognitive dysfunction and negative symptoms, whose etiology involves interactions between both genetic and environmental vulnerability factors. Recently, ongoing research attempting to elucidate the nature of these vulnerability factors has been generating exciting findings. The advances in understanding of environmental risk factors for mental illnesses and in genetic research into mental illnesses will be reviewed. Limitations of the findings and implications of these advances for genetic counseling practice will also be discussed.

The Genomic Era and Serious Mental Illness: A Potential Application for Psychiatric Genetic Counseling

Genetic counseling is an important clinical service that is routinely offered to families affected by genetic disorders or by complex disorders for which genetic testing is available. It is not yet routinely offered to individuals with serious mental illnesses and their families, but recent findings that beliefs about the cause of mental illness can affect an individuals adaptation to the illness suggest that genetic counseling may be a useful intervention for this population. In a genetic counseling session the counselor discusses genetic and environmental contributors to disease pathogenesis; helps individuals explore conceptions, fears, and adaptive strategies; and provides nondirective support for decision making. Expected outcomes may include reductions in fear, stigma, and guilt associated with a psychiatric diagnosis; improvements in adherence to prescribed medications; declines in risk behaviors; and reductions in misconceptions about the illness. The authors endorse a multidisciplinary approach in which a psychiatrist and genetic counselor collaborate to provide comprehensive psychiatric genetic counseling.

The genomic era and perceptions of psychotic disorders : Genetic risk estimation, associations with reproductive decisions and views about predictive testing

As a result of publicity surrounding genetic advances, increasing public awareness of a genetic role in major mental illness may be contributing to a “geneticization” of these illnesses. Geneticization could lead to oversimplified ideas about genetic risk, producing significant social consequences. We sought to investigate perceptions of genetic risk, associated effects on reproductive decisions and attitudes towards genetic testing amongst unaffected relatives of individuals with psychosis. A web‐based survey design was used, which all visitors to a psychosis support/information website had the option to complete. Responders were representative of website visitors, and the study design facilitated collection of a large dataset, although the response rate was low. Over‐estimating risk was associated with reproductive decisions favoring fewer children, and more positive attitudes towards genetic testing. Facilitating accurate risk perception through genetic counseling could significantly impact reproductive decisions, and the appropriate use of genetic tests in the future.

Conceptualizing Genetic Counseling as Psychotherapy in the Era of Genomic Medicine

Discussions about genetic contributions to medical illness have become increasingly commonplace. Physicians and other health-care providers in all quarters of medicine, from oncology to psychiatry, routinely field questions about the genetic basis of the medical conditions they treat. Communication about genetic testing and risk also enter into these conversations, as knowledge about genetics is increasingly expected of all medical specialists. Attendant to this evolving medical landscape is some uncertainty regarding the future of the genetic counseling profession, with the potential for both increases and decreases in demand for genetic counselors being possible outcomes. This emerging uncertainty provides the opportunity to explicitly conceptualize the potentially distinct value and contributions of the genetic counselor over and above education about genetics and risk that may be provided by other health professionals. In this paper we suggest conceptualizing genetic counseling as a highly circumscribed form of psychotherapy in which effective communication of genetic information is a central therapeutic goal. While such an approach is by no means new—in 1979 Seymour Kessler explicitly described genetic counseling as a “kind of psychotherapeutic encounter,” an “interaction with a psychotherapeutic potential”—we expand on his view, and provide research evidence in support of our position. We review available evidence from process and outcome studies showing that genetic counseling is a therapeutic encounter that cannot be reduced to one where the counselor performs a simple “conduit for information” function, without losing effectiveness. We then discuss potential barriers that may have impeded greater uptake of a psychotherapeutic model of practice, and close by discussing implications for practice.

Re-conceptualizing Risk in Genetic Counseling: Implications for Clinical Practice

Risk communication is an important component of genetic counseling. However, many authors have noted that after genetic counseling, subjective risk frequently does not match the objective risk provided by the counselor. This inevitably leads to the conclusion that the risk communication process was not “effective”. There has been much discussion about how this problem can be better addressed, such that our clients recall numeric risks more accurately after genetic counseling. This article draws on the risk and probability literature from other fields (including psychology, economics, philosophy and climate change) to deconstruct the concepts of “risk” and risk perception to attempt to expand upon and develop thought and discussion about and investigation of the risk communication process in genetic counseling.

Evaluating a unique, specialist psychiatric genetic counseling clinic: uptake and impact

People with psychiatric disorders and their family members have expressed interest in receiving genetic counseling (GC). In February 2012, we opened the first (to our knowledge) specialist psychiatric GC clinic of its kind, for individuals with non‐syndromic psychiatric disorders and their families. Prior to GC and at a standard 1‐month follow‐up session, clinical assessment tools are completed, specifically, the GC outcomes scale (GCOS, which measures empowerment, completed by all clients) and the Illness Management Self Efficacy scale (IMSES, completed by those with mental illness). Consecutive English‐speaking clients attending the clinic between 1 February 2012 and 31 January 2013 who were capable of consenting were asked for permission to use their de‐identified clinical data for research purposes. Descriptive analyses were conducted to ascertain demographic details of attendees, and paired sample t‐tests were conducted to assess changes in GCOS and IMSES scores from pre‐ to post‐GC. Of 143 clients, seven were unable to consent, and 75/136 (55.1%) consented. Most were female (85.3%), self‐referred (76%), and had personal experience of mental illness (65.3%). Mean GCOS and IMSES scores increased significantly after GC (p < 0.0001 and p = 0.011, respectively). In a naturalistic setting, GC increases empowerment and self‐efficacy in this population.

Applications and limitations of empiric data in provision of recurrence risks for schizophrenia: a practical review for healthcare professionals providing clinical psychiatric genetics consultations

Schizophrenia is a common disorder that may frequently be encountered when taking family histories in the genetics clinic, whether or not the referral is for a psychiatric indication. Like in other common disorders, the provision of recurrence risks for schizophrenia is a complex clinical issue because empiric recurrence risks (while reasonably well established) can rarely be used without individual tailoring. This review seeks to identify and detail some pertinent issues surrounding the clinical utility of empiric recurrence risks for schizophrenia, and to provide an overview of important factors to consider when tailoring empiric risks for individual patients.